The orphan receptor APJ (putative receptor protein related to angiotensin II type 1 receptor or AT1) is a G-protein coupled receptor with seven transmembrane domains, constituted of 380 amino acids. In the search for an endogenous ligand of the orphan receptor APJ, a peptide called apelin (APJ endogenous ligand) was first isolated from bovine stomach extracts and the corresponding human protein was deduced from this discovery.
The apelin polypeptide is initially produced as a 77 amino acid protein (called preproapelin) that is cleaved to produce cleavage products of 36 amino acids (proapelin), 17 amino acids, and 13 amino acids, each of them having a high affinity (in the nM range) for the APJ receptor. The peptide size of apelin-17 and apelin-13 are necessary and sufficient for the ability of an apelin polypeptide to interact with APJ. Currently, the mechanism and function of apelin precursor (proapelin or apelin-36) conversion to mature apelin peptides (apelin-17 or apelin-13) are not well known.
Apelin and APJ receptors are both widely distributed in the brain but are particularly highly expressed in the supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei. Dual labelling studies demonstrate that within these two nuclei, apelin and its receptor are colocalized with vasopressin (AVP) in a subset of magnocellular neurons. In lactating rats, characterized by increases in both synthesis and release of AVP, central injection of apelin inhibits the phasic electrical activity of AVP neurons, decreases systemic AVP release inducing aqueous diuresis. Taken together, these data suggest that apelin is a natural inhibitor of the antidiuretic effect of AVP. Moreover apelin systemically administered reduces arterial blood pressure, increases cardiac contractility and reduces cardiac loading.